1. Parkinson Disease:

3. Introduction

4. Levodopa: Gold Standard of Treatment for PD

5. Motor Complications With Initial Levodopa Therapy

6. Intermittent Oral Levodopa Dosing and Fluctuating Plasma Levodopa Levels

7. Levodopa-Related Motor Fluctuations in PD: Wearing Off

8. Classification of Levodopa-Related Motor Fluctuations in PD

9. Bothersome Symptoms in Advanced PD: The Patient's Perspective

10. Distribution of Non-Motor Symptoms in PD On/Off States

11. Clinical Case 1: A 67-Year-Old Man After 3 Years on Levodopa

12. Clinical Case 1: Motor and Non-Motor Symptoms During a Wearing Off Episode

13. Blocks to Oral Therapy: Poor Levodopa Absorption and Upper GI Pathologies

14. Treatment Options for Wearing Off in PD

15. Options and Objectives for Treating Wearing Off in PD

16. Mechanism of COMT Inhibition

17. COMT Inhibitors: Entacapone, Tolcapone, and Opicapone

18. Entacapone: Reduction in Off Time

19. Tolcapone: Reduction in Off Time

20. Opicapone: Background

21. BIPARK I: Change in Absolute Off Time in Hours

22. BIPARK Studies: Change in Absolute Off Time in Hours

23. Safety and Tolerability of Opicapone: 1-Year Open-Label Extension of BIPARK II

24. Clinical Case 2: A 63-Year-Old Man Diagnosed at 54 Years of Age

25. Clinical Case 2: Presenting Complaints

26. Clinical Case 2: Main Clinical Considerations

27. Clinical Case 2: Possible Treatment Options to Address Wearing Off

28. Clinical Case 2: Real Treatment Approach Used in This Patient

29. Clinical Case 3: A 78-Year-Old Woman With First Symptoms at Age 68 Years

30. Clinical Case 3: Early Treatment Approach

31. Clinical Case 3: Later Treatment Approach

32. Clinical Case 3: Main Clinical Considerations

33. Concluding Remarks

34. Abbreviations